2-fluoro-3-O-methoxymethyl-16β,17β-O-sulfonylestra-1,3,5(10)-triene-3,16β,17β-triol | 438459-01-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 2-fluoro-3-O-methoxymethyl-16β,17β-O-sulfonylestra-1,3,5(10)-triene-3,16β,17β-triol
• 英文别名: (1R,2S,4S,8R,9S,12S)-15-fluoro-16-(methoxymethoxy)-9-methyl-5,7-dioxa-6lambda6-thiapentacyclo[10.8.0.02,9.04,8.013,18]icosa-13,15,17-triene 6,6-dioxide；(1R,2S,4S,8R,9S,12S)-15-fluoro-16-(methoxymethoxy)-9-methyl-5,7-dioxa-6λ6-thiapentacyclo[10.8.0.02,9.04,8.013,18]icosa-13,15,17-triene 6,6-dioxide
• CAS: 438459-01-9
• 化学式: C₂₀H₂₅FO₆S
• 分子量: 412.479
• InChiKey: VWTJFFRJBLJDFQ-YUTQSESTSA-N

物化性质

• 沸点：
  537.6±50.0 °C(Predicted)
• 密度：
  1.325±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  79.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-fluoro-3-O-methoxymethyl-16β,17β-O-sulfonylestra-1,3,5(10)-triene-3,16β,17β-triol 在 硫酸 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 0.33h， 生成 2,16α-difluoroestradiol
  参考文献：
  名称：

  2,16α-和4,16α-二氟雌二醇及其11β-甲氧基衍生物的合成作为潜在的雌激素受体结合放射性药物

  摘要：

  我们通过两种不同的途径制备了2,16α-和4,16α-二氟雌二醇及其11β-甲氧基衍生物。第一条路线允许最终产品的大规模合成和表征，而第二条路线被选择用于氟化作用 作为便利的最后一步 贴标与寿命短的[ 18 F]氟。前一条路线涉及中间体双三甲基甲硅烷基烯醇醚和16α-氟雌酮的连续亲电氟化反应，然后进行减少异构体产物的17-酮分离和色谱分离。第二种途径是通过亲电取代雌酮或11β-甲氧基雌酮与N-氟吡啶鎓盐生成2-氟和4-氟衍生物，然后转化为反应性16β，17β-环硫酸盐。立体选择性开环硫酸盐 通过亲核的氟化作用使用Me 4 NF并随后去除保护层醚和硫酸盐基团通过快速水解 在酸性 乙醇得到所需的16α-氟衍生物。后一种方法可以容易地适于与放射性标记18通过取代我˚F 4 NF为18 ˚F -在乙腈。初步生物学数据表明，在16α-[ 18 F]氟雌​​二醇上同时添加了4-氟和11β-甲氧基（外语教学）可能会提供改进

  DOI：

  10.1039/b110021c
• 作为产物：
  描述：

  3,16β-diacetoxy-2-fluoroestra-1,3,5(10)-trien-17β-ol 生成 2-fluoro-3-O-methoxymethyl-16β,17β-O-sulfonylestra-1,3,5(10)-triene-3,16β,17β-triol
  参考文献：
  名称：

  Seimbille, Y.; Rousseau, J.; Benard, F., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S348 - S350

  摘要：

  DOI：

文献信息

• 18F-labeled difluoroestradiols: preparation and preclinical evaluation as estrogen receptor-binding radiopharmaceuticals
  作者：Yann Seimbille、Jacques Rousseau、François Bénard、Catherine Morin、Hasrat Ali、George Avvakumov、Geoffrey L Hammond、Johan E van Lier

  DOI：10.1016/s0039-128x(02)00025-9

  日期：2002.8

  A-ring fluorination of estradiol (ES) at position 2 or 4 decreases the rate of metabolism by blocking the formation of catechol estrogens, one of the major metabolic pathways of ES. We postulate that adding a 2- or 4-fluoro substituent to 16alpha-[F-18]fluoroestradiol (FES), a positron emission tomography (PET) radiopharmaceutical used for estrogen receptor (ER) imaging, should prolong its blood circulation time, and thus, improve its localization in ER-rich target tissues. On such account, we prepared a series of FES derivatives substituted with a fluorine atom at C2 or C4, with or without an 11beta-OMe group, and we tested their binding affinities for the ER and different serum proteins including rat alphafetoprotein (AFP) and human sex hormone-binding globulin (SHBG). Labeling at the 16alpha-position was accomplished via nucleophilic substitution with [F-18]F- on the reactive 16beta,17beta-cyclic sulfate intermediates. Decay corrected yields varied between 30 and 50% for a total synthesis time of 120 min, providing final products with specific activities >3000 Ci/mmol. The F-18-labeled analogs were evaluated for their biodistribution in immature female rats. Substitutions with the 4-F have little effect on binding affinities. Addition of the 2-F diminishes ER and AFP-binding affinities while augmenting the affinity for the SHBG. Addition of the 11beta-OMe decreases all binding affinities, particularly to AFP and SHBG. In contrast, biodistribution of the corresponding [16alpha-F-18]fluoro analogs in immature female rats revealed that the presence of the 11beta-OMe group improves ER-mediated uterus uptake, with the 4,16alpha-[16alpha-F-18]difluoro-11beta- methoxyestradiol showing the highest uptake values (15% ID at 1-h post-injection). These data suggest that the addition of both a 4-F and 11beta-OMe group onto FES may provide an improved radiopharmaceutical for PET imaging of ER densities in breast cancer patients. (C) 2002 Elsevier Science Inc. All rights reserved.
• Seimbille, Y.; Rousseau, J.; Benard, F., Journal of labelled compounds and radiopharmaceuticals, 2001, vol. 44, p. S348 - S350
  作者：Seimbille, Y.、Rousseau, J.、Benard, F.、Ali, H.、Lier, J. E. van

  DOI：——

  日期：——
• Synthesis of 2,16α- and 4,16α-difluoroestradiols and their 11β-methoxy derivatives as potential estrogen receptor-binding radiopharmaceuticals
  作者：Yann Seimbille、Hasrat Ali、Johan E. van Lier

  DOI：10.1039/b110021c

  日期：2002.2.22

  fluorinations of intermediate bistrimethylsilyl enol ethers and 16α-fluoroestrones followed by reduction of the 17-ketone and chromatographic separation of the isomeric products. The second route proceeds via electrophilic substitution of estrone or 11β-methoxyestrone with N-fluoropyridinium salt to give the 2- and 4-fluoro derivatives followed by conversion to the reactive 16β,17β-cyclic sulfates. Stereoselective

  我们通过两种不同的途径制备了2,16α-和4,16α-二氟雌二醇及其11β-甲氧基衍生物。第一条路线允许最终产品的大规模合成和表征，而第二条路线被选择用于氟化作用 作为便利的最后一步 贴标与寿命短的[ 18 F]氟。前一条路线涉及中间体双三甲基甲硅烷基烯醇醚和16α-氟雌酮的连续亲电氟化反应，然后进行减少异构体产物的17-酮分离和色谱分离。第二种途径是通过亲电取代雌酮或11β-甲氧基雌酮与N-氟吡啶鎓盐生成2-氟和4-氟衍生物，然后转化为反应性16β，17β-环硫酸盐。立体选择性开环硫酸盐 通过亲核的氟化作用使用Me 4 NF并随后去除保护层醚和硫酸盐基团通过快速水解 在酸性 乙醇得到所需的16α-氟衍生物。后一种方法可以容易地适于与放射性标记18通过取代我˚F 4 NF为18 ˚F -在乙腈。初步生物学数据表明，在16α-[ 18 F]氟雌​​二醇上同时添加了4-氟和11β-甲氧基（外语教学）可能会提供改进